Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

rTNF was administered to 28 patients with advanced metastatic cancers by continuous intravenous infusion for 5 consecutive days every 2 weeks. The dose levels were 30, 40, 70, 110, 180 and 290 micrograms/M2/day. Groups of 3 patients were started at each successive dose level and then on subsequent courses treated with the next dose level through 4 escalations as tolerated. Tumor types were: colon cancer 14; adenocarcinoma of unknown primary, 2; renal cancer, 2; leiomyosarcoma, 2; lung cancer, 1; prostate cancer, 1; thymona, 1; bladder cancer; 1; parotid, 1; Kaposi's sarcoma 2; ovarian 1. Toxicities included fever and chills (usually within the first 8 hours of infusion), fatigue, headache, decreased performance status, hypotension and CNS. All patients experienced leukopenia and thrombocytopenia within 24 hours or less after start of infusion with return of baseline by 72 hours after rTNF was stopped. The fall in these counts averaged 50% and was not dose related. No major changes in liver or renal function, coagulation or blood lipids were seen. Major dose limiting toxicities were fatigue, confusion, thrombocytopenia, seizures, hypotension and decreased performance status. NK cell activity measured against K562 target cells was augmented from about 30% target cell lysis to about 70% target cell lysis over the first 7 days of treatment. Two patients, both with metastatic colon cancer showed transient, objective tumor regression which did not qualify as a partial response. One patient with ovarian cancer had a stable partial response but progressed after 13 courses of treatment. Continuous infusion of TNF can be safely administered to patients with a maximum tolerated dose of only between 30 and 40 micrograms/M2/day.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A phase I trial of recombinant tumor necrosis factor (rTNF) administered by continuous intravenous infusion in patients with disseminated malignancy. 264 24

The Kampala Cancer Registry (KCR), in Kyadondo County, Uganda, was established in 1951. During 1972-87, KCR activity was reduced because of the Ugandan political situation. Reactivation of the KCR has provided data on incidence in Kyadondo County residents from September 1989 to December 1991. Kyadondo County had just over 1 million residents (living there at least 1 year) in 1991. Data sources were the records of the Department of Histopathology, which receives KCR registration information along with specimens, and hospital records verified by a cancer registrar from the 4 major county hospitals. (Death certificates are not available at present in Uganda). These data were compared with those reported in 1954-60 and 1968-70 to determine changes in cancer incidence in an era marked by changing lifestyles and the emerging AIDS epidemic. 558 males and 675 females were registered in the 28-month period. Data were tabulated separately for males and females, showing number of cases/site and average annual age-specific incidence rates. Age-standardized incidence rates were compared for 1989-91, 1954-68, 4 other African population-based series, and White and Black US population rates. The most frequent 1981-91 cancers for men were Kaposi's sarcoma, 48.6% esophagus, 6.9%; nonHodgkin's lymphoma (NHL), 6.2%; prostate, 5.5%; and liver, 4.9%. In women, the most frequent cancers were cervical, 32.1% in the highest record in Africa; Kaposi's sarcoma, 17.9%; and breast cancer, 11.4%. A comparison to earlier KCR data revealed that incidence of Kaposi's sarcoma has increased from 2.6 to 30.1/100,000 in men and from 0 to 11/100,000 in women. This finding is clearly related to the AIDS epidemic. However, the rate of NHL, which is an increased risk for US AIDS patients, has shown little change. However, the incidence of NHL (specifically Burkitt's) in KCR children 0-14 years old is relatively high (19/1/million in boys and 12.1/million in girls), and the AIDS epidemic may be responsible, although much remains to be discovered about AIDS-related NHL, particularly Burkitt's. Incidence increases were found in men for esophageal and prostate cancer, whereas cases of cancer of the penis and bladder declined. In women, the incidence of cervical cancer doubled since the 1950s. Breast cancer, while the third most common, shows the typical low, rate of a low-birth population, although the rate has doubled since 1954-60.
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PMID:Cancer in Kampala, Uganda, in 1989-91: changes in incidence in the era of AIDS. 847 45

Persons with human immunodeficiency virus/AIDS are at high risk of Kaposi's sarcoma (KS), non-Hodgkin lymphoma (NHL), and possibly anal cancers. To examine whether this risk preceded the AIDS epidemic, we used pre-AIDS era data from the Surveillance, Epidemiology, and End Results program (excluding Connecticut) from 1973 to 1976, and the Connecticut Tumor Registry from 1940 to 1976. We compared risk of being single (a surrogate to identify men who might be homosexual) to those ever married, using a case control matching study with up to 10 controls per case. Overall, no excess risk was observed for KS (risk ratio for men 20-59 years old: 1.00; 95% confidence interval 0.218-3.61), but there was a suggestion of higher risk (4.00; 0.54-29.48) in 1973-1976, the period just before the AIDS epidemic. The NHL risk (0.85; 0.74-0.99) was slightly low, but for anal cancer the risk ratio of being single was significantly high both in men 20-59 years old (5.68) and older men (2.78) long before the AIDS epidemic. If the excess risk was solely due to being homosexual, the actual relative risk in the subset who were homosexual must have been much higher, given that only a fraction of the single men would have been homosexual. As comparison groups to verify the methodology, we used colon (no association with marital status) and prostatic cancer (decreased in single men), with findings as reported in other studies. Thus, single men may have been at an excess risk of KS (but a slightly low risk of NHL) just before the AIDS epidemic and have been at excess risk of anal cancer for many years before the AIDS epidemic.
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PMID:Marital status in relation to Kaposi's sarcoma, non-Hodgkin's lymphoma, and anal cancer in the pre-AIDS era. 855

Although the incidence of classic Kaposi's sarcoma (CKS) has been investigated, its occurrence following a primary neoplasm and its association with this first neoplasm need to be determined. We analyzed a series of 124 patients with a secondary CKS (8.4% of a total of 1485 incident cases) which occurred between 1961 and 1992 in the Jewish Israeli population. Data on first neoplasms and subsequent Kaposi's sarcoma were retrieved from the Israel Cancer Registry. Acquired-immune-deficiency-syndrome-related Kaposi's sarcomas were excluded from the case series. Four controls were randomly selected for each CKS case among all Cancer Registry cases free from a second neoplasm at the time of diagnosis of the CKS in the case, and matched on gender, year of birth and year of diagnosis of the first neoplasm. The average time lapse between first neoplasm and secondary CKS was 4.5 years, being shorter for prostate cancer and for hematopoietic malignancies. As compared with Israel-born Jews, the risk of a subsequent CKS was significantly increased in immigrants [odds ratio (OR) 3.0]; this risk was particularly high in immigrants from the former Soviet Union (OR 9.4) and Poland (OR 7.0). There was no clear trend with age at immigration; however, low age at immigration and a short length of stay in Israel endowed a higher risk of developing a secondary CKS, markedly among patients suffering from solid tumors as the first primary. There was an excess of secondary CKS following a non-Hodgkin's lymphoma (OR 5.3), a Hodgkin's lymphoma (OR 7.5), a leukemia (OR 5.3) or a breast cancer (OR 2.2). Cancer patients with a first primary in the lung, colon, stomach, larynx, liver, pancreas or kidney showed secondary CKS less frequently. Despite the lack of control of therapy for the first neoplasm, development of secondary CKS seems to be mediated by mechanisms similar to those for hematopoietic neoplasms and selected nonhematopoietic neoplasms, such as breast cancer. The trend toward increased risk after a short time lapse and the difference in risk among immigrants indicate that genetic susceptibility is part of the complex interplay between cellular proliferation and control systems.
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PMID:Classic Kaposi's sarcoma as a second primary neoplasm. 993 96

Human herpesvirus 8 (HHV-8, also called KSHV) is linked to the etiopathogenesis of Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion lymphoma (PEL). The universal presence of HHV-8 in early KS has not yet been shown. We used a mAb (LN53) against latent nuclear antigen-1 (LNA-1) of HHV-8 encoded by ORF73 to study the distribution of the cell types latently infected by HHV-8 in patch, plaque, and nodular KS, MCD, and PEL. In early KS, HHV-8 is present in <10% of cells forming the walls of ectatic vessels. In nodular KS, HHV-8 is present in cells surrounding slit-like vessels and in >90% of spindle cells, but not in normal vascular endothelium. In addition, HHV-8 colocalizes with vascular endothelial growth factor receptor-3 (VEGFR-3), a marker of lymphatic and precursor endothelium. In early KS lesions, VEGFR-3 is more extensively expressed than LNA-1, indicating that HHV-8 is not inducing the proliferation of VEGFR-3-positive endothelium directly. In MCD, HHV-8 is present in mantle zone large immunoblastic B cells. No staining for LNA-1 is seen in samples from multiple myeloma, prostate cancer, and angiosarcoma, supporting the absence of any etiological link between these diseases and HHV-8.
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PMID:Distribution of human herpesvirus-8 latently infected cells in Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma. 1020 Feb 99

Doxil, a doxorubicin formulation of polyethylene glycol-coated liposomes, has anti-tumor activity against Kaposi's sarcoma and other solid tumors with mild myelosuppression, minimal hair loss and a low risk of cardiotoxicity. Non-liposomal doxorubicin has modest activity in hormone-refractory prostate cancer (HRPC) with considerable toxicity. A pilot study of Doxil was conducted in 15 patients with HRPC. Doxil was administered i.v. using two regimes of equal dose intensity, either 45 mg/m2 every 3 weeks or 60 mg/m2 every 4 weeks. Plasma levels of doxorubicin were analyzed in 10 patients. The most common side effect was stomatitis with a higher incidence at the 60 mg/m2 dose level. In contrast, hand-foot syndrome was more frequent and severe in patients treated with the 3 week schedule of 45 mg/m2. Three patients responded to treatment (based on objective response in one patient and reduction of PSA level greater than 50% in the other two) and two patients had stable disease, all of them receiving 60 mg/m2. Pharmacokinetic analysis shows a proportional increase of plasma drug levels with dose and the characteristic long circulation time of Doxil with half-lives in the range of 3 days, somewhat longer than previously reported. In conclusion, Doxil at 60 mg/m2 every 4 weeks appears to be active against HRPC, but severe mucocutaneous toxicities prevented further investigation of this regime.
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PMID:Doxil (Caelyx): an exploratory study with pharmacokinetics in patients with hormone-refractory prostate cancer. 1078 95

TNP-470, an analogue of fumagillin, has been shown to inhibit angiogenesis in vitro and in vivo. In 1992, TNP-470 entered clinical development for cancer as an anti-angiogenic agent. It is currently in Phase I/II trials in Kaposi's sarcoma, renal cell carcinoma, brain cancer, breast cancer, cervical cancer and prostate cancer. In early clinical reports, TNP-470 is tolerated up to 177 mg/m(2) with neurotoxic effects (fatigue, vertigo, ataxia, and loss of concentration) being the principal dose limiting toxicity (DLT). Terminal half-life values are short and have shown intermittent and intrapatient variation (range: 0.05 - 1.07 h). Recently, mechanistic studies have identified cell cycle mediators and the protein methionine aminopeptidase-2 (MetAP-2) as molecular targets of TNP-470 and fumagillin. Animal studies confirm some toxic effects on normal angiogenic processes such as the female reproductive system and wound healing, which will require caution and close monitoring in the clinic. TNP-470 is one of the first anti-angiogenic compounds to enter clinical trials, making it a valuable prototype for future trials of angiogenesis inhibitors in oncology.
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PMID:TNP-470: an angiogenesis inhibitor in clinical development for cancer. 1106 Jul 50

The breakthrough discovery of the anti-angiogenic effects of thalidomide gave impetus to a series of clinical trials in patients with solid tumors and hematologic malignancies. Thalidomide has been shown to block the activity of angiogenic substances like bFGF, VEGF and interleukin 6. This drug also down-regulates TNF alpha. Thalidomide has shown clinical antitumor activity in single-agent, phase II clinical trials in AIDS-related Kaposi sarcoma, glioma, multiple myeloma refractory to chemotherapy, and hormone-refractory prostate cancer. In contrast, thalidomide was inactive in breast, lung and kidney cancer. The dose-limiting toxicity of thalidomide is sedation. Other adverse effects include skin rash, constipation, dry mouth and liver function abnormalities, along with peripheral neuropathy and the drug's well-known teratogenic potential. The advantages of thalidomide include the convenience of the oral route of administration, the drug's toxicity profile--substantially milder than that of chemotherapy--and its low cost. The potential role of thalidomide in the treatment of human neoplasia will be confirmed by means of randomized clinical trials.
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PMID:[Thalidomide. Clinical trials in cancer]. 1118 34

Thalidomide--removed from widespread clinical use by 1962 because of severe teratogenicity--has antiangiogenic and immunomodulatory effects, including the inhibition of tumor necrosis alpha factor. It has now returned to practice as an effective oral agent in the management of various disease states including erythema nodosum leprosum, for which it was approved by the U.S. Food and Drug Administration in 1998, and more recently certain malignancies, including multiple myeloma. Although thalidomide's mechanism of action remains incompletely understood, considerable insight has been generated by extensive preclinical studies in multiple myeloma. Moreover, clinical trials have confirmed benefit in relapsed disease, and the role of thalidomide in treating newly diagnosed patients is currently under study. Its use in other tumors is under evaluation, with promise in renal cell carcinoma, prostate cancer, glioma, and Kaposi's sarcoma. Activity has also been demonstrated in chronic graft-versus-host disease and in symptom relief as part of palliative care.
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PMID:Thalidomide: emerging role in cancer medicine. 1181 93

Classification of lymphedema is debated, because authors don't agree with the disordered physiology. Kinmonth divided all cases into primary and secondary lymphedema. Three types of primary lymphedema have been recognized: congenital, precox and tarda. Secondary lymphedema develops as a consequence of disruption or obstruction of the lymphatic pathways. Iatrogenic lymphedema are caused by surgery and/or radiation therapy. Post-infectious lymphedema are mainly caused by filariasis in tropical areas, and by cellulitis in occidental areas. Neoplastic disease (breast, prostatic cancer, Kaposi's sarcoma) are a major cause of secondary lymphedema. Less frequent etiologies are rheumatoid lymphedema, pathomimic lymphedema, pretibial myxoedema. Reduced lymphatic drainage is associated with severe chronic venous insufficiency and contributes to the leg swelling and the risk of infection.
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PMID:[Classification of lymphedema]. 1216 99


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